Study finds gene bringing together animal and human research in alcoholism

Apr 23, 2009

An important genetic study conducted through Mayo Clinic has identified vital new information concerning alcoholism in subjects with European ancestry, according to a recent issue of Alcohol: Clinical and Experimental Research.

Research findings indicate that is highly inheritable, although specific genes and their variations associated with this illness remain unknown. studies allow identification of potential candidate genes but their relevance to alcoholism in humans and its complications, including alcohol withdrawal and , require additional research. Under the direction of Victor Karpyak, M.D., Ph.D., of the Mayo Clinic Department of Psychiatry and Psychology, a team of clinical and basic scientists investigated the sequence of the human MPDZ gene and its association with risks for alcohol dependence and alcohol withdrawal seizures.

"We have long known that the presence of severe withdrawal and seizures indicates strong physical dependence on alcohol," states Dr. Karpyak. "Focus on this group of subjects increases our chances to successfully identify the genetic variations associated with alcoholism in general and the presence of withdrawal symptoms specifically."

Sophisticated genetic research in mice isolated small regions on mouse chromosomes linked to severity of acute alcohol and barbiturate withdrawal measured by the presence and severity of seizures. Further research demonstrated that MPDZ gene is the only one in this chromosome region which has variants associated with severity of acute alcohol and barbiturate withdrawal and seizures.

The MPDZ protein is an important scaffolding , responsible for synaptic structure and plasticity. It is also known to be involved in and as well as seizures and and, thus, is a good candidate for the human study focused on genetic predictors for alcohol withdrawal. Unfortunately, little was known about sequence variability of the MPDZ gene in humans. It is also a very long gene and its sequencing required considerable effort and costs.

To investigate the relevance of the model findings in animals for human alcoholism, Dr. Karpyak and his collaborators resequenced the human MPDZ gene in 61 subjects with a history of alcohol withdrawal seizures, 59 subjects with a history of withdrawal without seizures and 64 samples from non-alcoholic subjects -- all with European American ancestry. Sixty-seven new, mostly rare variants were discovered in the human MPDZ gene. Sequencing allowed the first opportunity of comparing the MPDZ gene in humans and mice. The new Mayo study found that the human gene does not have variations identical to those comprising the MPDZ gene associated with alcohol withdrawal seizures in mice.

Second, researchers used common variants to compare haplotype structure of the MPDZ gene in alcohol dependent subjects with and without history of withdrawal seizures and in controls who did not have alcoholism. The study revealed a significant association between MPDZ gene variant alcohol-dependency without seizures, compared to the control subjects. Contrary to initial hypothesis and animal findings, the study showed no significant association between MPDZ sequence variants and withdrawal seizures in humans. This suggests the potential role of MPDZ in alcoholism and/or related phenotypes other than alcohol withdrawal seizures.

This important new information supports further investigation of the role of MPDZ gene in alcoholism and its complications including withdrawal syndrome. It also indicates the importance of close collaboration between clinical and basic scientists that could provide critical insights into the mechanism of the association and reveal significant genetic markers of alcoholism.

Source: Mayo Clinic (news : web)

Explore further: Quality control for adult stem cell treatment

add to favorites email to friend print save as pdf

Related Stories

Brain DNA 'remodeled' in alcoholism

Apr 02, 2008

Reshaping of the DNA scaffolding that supports and controls the expression of genes in the brain may play a major role in the alcohol withdrawal symptoms, particularly anxiety, that make it so difficult for alcoholics to ...

Scientists identify gene that influences alcohol consumption

Dec 05, 2007

A variant of a gene involved in communication among brain cells has a direct influence on alcohol consumption in mice, according to a new study by scientists supported by the National Institute on Alcohol Abuse and Alcoholism ...

Brain chemistry ties anxiety and alcoholism

Mar 04, 2008

Doctors may one day be able to control alcohol addiction by manipulating the molecular events in the brain that underlie anxiety associated with alcohol withdrawal, researchers at the University of Illinois at Chicago College ...

Recommended for you

Quality control for adult stem cell treatment

1 hour ago

A team of European researchers has devised a strategy to ensure that adult epidermal stem cells are safe before they are used as treatments for patients. The approach involves a clonal strategy where stem cells are collected ...

A gene for brain size only found in humans

4 hours ago

About 99 percent of human genes are shared with chimpanzees. Only the small remainder sets us apart. However, we have one important difference: The brain of humans is three times as big as the chimpanzee ...

Experts warn of stem cell underuse

10 hours ago

Since the first experimental bone marrow transplant over 50 years ago, more than one million hematopoietic stem cell transplantations (HSCT) have been performed in 75 countries, according to new research charting the remarkable ...

Longer needles recommended for epinephrine autoinjectors

21 hours ago

(HealthDay)—Given the increasing epidemic of obesity, epinephrine autoinjectors (EAIs) for anaphylaxis require longer needles to ensure intramuscular injection, according to a study published online Feb. ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.